Lipolytic modification of LDL by phospholipase A(2) induces particle aggregation in the absence and fusion in the presence of heparin

One of the first events in atherogenesis is modification of low density Lip oprotein (LDL) particles in the arterial wall with ensuing formation of agg regated and fused lipid droplets. The accumulating particles are relatively depleted in phosphatidylcholine (PC). Recently, secretory phospholipase A( 2) (PLA(2)), an enzyme capable of hydrolyzing LDL PC into fatty acid and ly soPC molecules, has been found in atherosclerotic arteries. There is also e vidence that both LDL and PLA(2) bind to the glycosaminoglycan (GAG) chains of extracellular proteoglycans in the arterial wall. Here we studied the e ffect of heparin GAG on the lipolytic modification of LDL by PLA(2). Untrea ted LDL, heparin-heated LDL, and heparin-bound LDL were lipolyzed with bee venom PLA(2). In the presence of albumin, lipolysis resulted in aggregation in all 3 preparations of the LDL particles. Lipolysis of untreated LDL did not result in aggregation if albumin was absent from the reaction medium, and the lipolytic products accumulated in the particles rendering them nega tively charged. However, heparin-treated and heparin-bound lipolyzed LDL pa rticles aggregated even in the absence of albumin. Importantly, in the pres ence of albumin, some of the heparin-treated and heparin-bound lipolyzed LD L particles fused, the proportion of fused particles being substantially gr eater when LDL was bound to heparin during lipolysis. In summary, lipolysis of LDL PC by PLA(2) under physiological conditions, which allow transfer o f the lipolytic degradation products to albumin, leads to fusion of LDL par ticles in the presence, but not in the absence, of heparin. Thus, it is pos sible that within the GAG meshwork of the arterial intima, PLA(2)-induced m odification of LDL is one source of the lipid droplets during atherogenesis .